The ability to non-destructively measure trabecular bone strength and microdamage would have a profound effect in bone biomechanics research. It would enable researchers to assess bone strength longitudinally in animal models, and determine the strength behavior of bone repeatedly in the same specimen for various different types of loading cases and under simulation of various types of treatment, including drug and exercise effects. It would also greatly facilitate the study of microdamage in bone since currently this is an extremely tedious process. We propose here a method to perform such non-invasive assessment of trabecular bone strength and microdamage. This method can also be used to measure the failure properties of trabecular hard tissue material, a unique indicator of trabecular quality. The basis of this technology is the "high-resolution" finite element computer modeling technique, in which the models are derived from micro-computed tomography (micro-CT) images having spatial resolutions on the order of microns. Specifically, we plan to incorporate into these models the physics of large deformations. This will enable us to simulate the correct deformation patterns that occur in individual trabeculae when loaded to failure. We have evidence that inclusion of such behavior is crucial to the ability of such models to properly capture the strength behavior of trabecular bone of any density, but particularly at low density. To validate the models, we will also develop an automated technique for the direct three-dimensional quantification of trabecular microdamage, itself a substantial technical innovation that will greatly impact research on bone microdamage. In achieving our goal, we will test two hypotheses. First, we hypothesize that the failure strains of trabecular tissue material are independent of anatomic site even though the failure strains of the whole specimen (apparent level) are not. The reason for this is the large deformation effect, which is manifested in some sites due to the low bone density. Second, we hypothesize that microdamage within trabecular bone can be predicted based on the magnitude of the strains within the trabecular tissue. This is based on the assumption that tissue level damage occurs when the site-independent tissue failure strains are exceeded. Should this be true, it will enable researchers to use these types of computer models to study both the development and biomechanical effects of microdamage in trabecular bone at a level of detail so far unthinkable. This R21 project represents an important technological foundation for improving understanding of the failure mechanisms in trabecular bone, with particular applications to aging and osteoporosis. Specifically, by addressing strength at the whole specimen and trabecular tissue levels, as well as microdamage and large deformation architectural effects, this work will provide a comprehensive and unique approach to assessment of trabecular bone strength and quality.